Fractional Flow Reserve: Basics, FAME 1, FAME 2 William F. Fearon, MD Associate Professor Stanford University Medical Center
Conflict of Interest Advisory Board for HeartFlow Research grant from St. Jude Medical Research and salary support from National Institutes of Health: 1 R01 HL093475 (PI)
Fractional Flow Reserve Proximal Pressure (Pa) Distal Pressure (Pd) FFR = P d / P a during maximal flow P a P d / P a = 60 / 100 FFR = 0.60 P d
Unique Aspects of FFR Clearly defined normal value Not affected by resting hemodynamics Relatively easy to perform Adapted from: Pijls and De Bruyne, Coronary Pressure Kluwer Academic Publishers, 2000
Validation of FFR Fractional Flow Reserve Exercise Test Thallium Scan Stress Echo 0.75 FFR < 0.75 : Sensitivity = 88% Specificity = 100% Pijls et al., New Engl J Med 1996;334:1703
Safety of Deferring PCI Based on FFR 5 Year Cardiac Death and Acute MI rate in DEFER trial 20 % 15 10 P=0.20 P< 0.003 P< 0.005 15.7 7.9 5 3.3 0 DEFER PERFORM REFERENCE FFR 0.75 FFR < 0.75 Pijls, et al. J Am Coll Cardiol 2007;49:2105-11
FFR and the Grey Zone De Bruyne, et al. Circulation 2001;104:157-62
FFR and the Grey Zone Sensitivity Specificity FFR=0.75 0.80 De Bruyne, et al. Circulation 2001;104:157-62
Grey Zone
Performing FFR:
Performing FFR: 1. IC NTG and IV heparin/bivalirudin 2. Equalize Pressures
Performing FFR Wiring the Lesion Distal end of wire Consider disconnecting the wire from the interface connector Can use exchange catheter to more safely position pressure wire Interface connector
Performing FFR Inducing Hyperemia Intravenous Infusion (Preferably Central Line) - Adenosine 140 µg/kg/min Intracoronary Bolus LCA RCA - Papaverine 12 mg 8 mg - Adenosine 16 µg 12 µg 100 µg!
Performing FFR Pressure Pullback Focal LAD Lesion Distal LAD Proximal Edge of LAD lesion
Performing FFR Pullback in Moderately and Diffusely Diseased LAD Distal LAD Proximal LAD
Performing FFR Recognizing Drift True Gradient Drift
Why do we need FFR? Nuclear perfusion scans performed in > 5000 patients Medical Therapy Revascularization Cardiac Death (%/yr) 5 4 3 2 1 0 4.6 2.3 1.3 1.1 0.8 0.9 0.3 0 Nl Mild Abnl Mod Abnl Sev Abnl Nuclear Scan Result Hachamovitch, et al. Circulation 1998;97:535-543
JAMA 2008;300:1765
Limitation of Noninvasive Imaging 143 Patients with angiographically significant 3 vessel disease (> 70% diameter stenosis) Thallium Scan Finding % Patients No Defect 18% Single Vessel Pattern 36% Two Vessel Pattern 36% Three Vessel Pattern 10% Lima et al. J Am Coll Cardiol 2003;42:63-70
Limitation of Angiography Comparison of QCA to FFR in over 3,000 lesions 1.0 (-) Ischemia 0.9 0.8 0.7 0.6 FFR 0.5 0.4 0.3 0.2 0.1 (+) Ischemia 0.0 0 10 20 30 40 50 60 70 80 90 100 Diameter Stenosis (%) Courtesy of Bernard De Bruyne, MD, PhD
Why FFR instead of IVUS? IVUS FFR
MLA = 4.98 mm2
FFR = 0.75 Resting Hyperemia
Disconnect between Anatomy and Physiology 50% Stenosis FFR=0.85 Myocardium Collaterals Collateral-Supplied Myocardium 50% Stenosis FFR=0.75 Vessel-Supplied Myocardium During Maximal Hyperemia
IVUS Evaluation of Intermediate Lesions Comparison Threshold Briguori, et al. (AJC 2001) FFR MLA < 4.0 mm 2 Takagi, et al. (Circ 1999) FFR MLA < 3.0 mm 2 Kang, et al. (Circ CVI 2011) FFR MLA < 2.4 mm 2
Determinants of an Abnormal FFR Braunwald s Heart Disease 2005, 7 th edition, vol.2, p.1112.
Why do we need FFR? Fractional Flow Reserve versus Angiography for Multivessel Evaluation New Engl J Med 2009;360:213-24
FAME Trial: FFR-Guided PCI performed on indicated lesions only if FFR 0.80 Lesions warranting PCI identified Randomized Angio-Guided PCI performed on indicated lesions Primary Endpoint Composite of death, MI and repeat revasc. (MACE) at 1 year New Engl J Med 2009;360:213-24.
FAME-like Case Example: 46 year old diabetic woman with HTN and dyslipidemia presents to outside hospital with a NSTEMI. Cath reveals 3 vessel CAD and the patient is transferred to Stanford for CABG. Cardiac surgeon reviews angiogram and asks for a second opinion.
FFR of RCA = 0.87 Resting Hyperemia
FFR of Ramus = 0.97 Hyperemia
Summary of Case Anatomic 3V CAD, functional 1V CAD Successfully treated with single stent 130 cc contrast, < 1 hour procedure Remains event free at > 12 months
Angio- Guided n = 496 FFR- Guided n = 509 P Value Indicated lesions / patient 2.7±0.9 2.8±1.0 0.34 Stents / patient 2.7 ± 1.2 1.9 ± 1.3 <0.001
Angio- Guided n = 496 FFR- Guided n = 509 P Value Indicated lesions / patient 2.7±0.9 2.8±1.0 0.34 Stents / patient 2.7 ± 1.2 1.9 ± 1.3 <0.001 Procedure time (min) 70 ± 44 71 ± 43 0.51 Contrast agent used (ml) 302 ± 127 272 ± 133 <0.001 Equipment cost (US $) 6007 5332 <0.001 Length of hospital stay (days) 3.7 ± 3.5 3.4 ± 3.3 0.05
FAME Study: One Year Outcomes % 20 Angio-Guided FFR-Guided ~30% 18.3 15 10 5 ~40% 3 1.8 ~35% 8.7 5.7 ~30% 9.5 6.5 ~35% 11.1 7.3 13.2 0 Death MI Repeat Revasc Death/MI p=0.04 MACE p=0.02 New Engl J Med 2009;360:213-24.
FAME Study: Two Year Outcomes Death/MI was significantly reduced from 12.9% to 8.4% (p=0.02) Survival Free of MACE FFR-Guided Angio-Guided 730 days 4.5% Pijls, et al. J Am Coll Cardiol 2010;56:177-184
FFR and Acute Coronary Syndromes 328 of the 1,005 patients in FAME had UA or NSTEMI Sels, et al. J Am Coll Cardiol Intv 2011;4:1183-9.
FAME: Economic Evaluation Bootstrap Analysis FFR-guided PCI saved >$2,000 per patient at one year compared to Angioguided PCI Fearon, et al. Circulation 2010;122:2545-50.
What happens to deferred lesions? 513 Deferred Lesions in 509 FFR-Guided Patients 2 Years Two Year Follow-up of Lesions Deferred in FAME 31 Myocardial Infarctions 22 Peri-procedural 9 Late Myocardial Infarctions 8 Due to a New Lesion or Stent-Related 1 Myocardial Infarction due to an Originally Deferred Lesion Only 1/513 or 0.2% of deferred lesions resulted in a late myocardial infarction Pijls, et al. J Am Coll Cardiol 2010;56:177-84
Which Lesions Need FFR? 1329 lesions in the FFR-guided arm ~20% ~35% Need FFR Tonino, et al.j Am Coll Cardiol 2010;55:2816-21.
Anatomic vs. Functional CAD 0VD (9%) 3VD (14%) Angiographic 3 Vessel 1VD (34%) 2VD (43%) Disease Tonino, et al. J Am Coll Cardiol 2010;55:2816-21
SYNTAX Score Angiography-based scoring system aimed at determining coronary lesion complexity Calcification Dominance No. & Location of lesion Left Main Because it is angiographybased, it is inherently limited by the accuracy of the coronary angiogram Thrombus Bifurcation SYNTAX SCORE CTO 3 Vessel Tortuosity
Outcomes Based on Syntax Score Worse outcomes with PCI vs CABG with higher SYNTAX score >22 33 Serruys, et al. N Engl J Med 2009;360:961-72
Outcomes Based on Syntax Score Similar outcomes with PCI vs CABG with lower SYNTAX score 0-22 Serruys, et al. N Engl J Med 2009;360:961-72
Impact of SYNTAX Score on PCI Recently published European guidelines for revascularization Wijns W, Kolh P, et al. Eur Heart J 2010;31:2501-55
Can we enhance the SYNTAX Score? By incorporating FFR into the SYNTAX score, termed Functional SYNTAX Score (FSS), can we: Convert high/medium risk SYNTAX score patients to a lower risk group? Improve our risk stratification of patients with multivessel CAD undergoing PCI?
FSS Reclassifies > 30% of Cases Without FFR Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8
FSS Reclassifies > 30% of Cases Without FFR With FFR Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8
FSS Discriminates Risk for Death/MI P < 0.01 Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8
FSS Discriminates Risk for MACE P < 0.01 P < 0.001 Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8
Effect of FSS in Multivessel CAD The mean FSS decreased by ~25% compared to the mean SS 43% of patients with a SS > 22 moved to an FSS < 22 Nam CW, et al. J Am Coll Cardiol 2011;58:1211-8
FSS Case: Mr. H. 79 year old retired physicist with angina Risk factors include HTN and dyslipidemia Stress echo revealed anteroseptal and apical ischemia Referred for coronary angiography on September 10 th, 2010
How should we handle this case? Recently published European guidelines for revascularization Calculated SYNTAX score = 25.5 Wijns W, Kolh P, et al. Eur Heart J 2010; 31:2501-55
FFR of RCA = 0.91
How should we handle this case? Recently published European guidelines for revascularization Recalculated SYNTAX score after FFR = 18.5 Wijns W, Kolh P, et al. Eur Heart J 2010; 31:2501-55
e-mail from Mr. H. Sept. 19 th, 2010: Dr. Fearon...this is from New Mexico. Yesterday we were walking around on the base of the Santa Fe ski area at over 10,300 feet. Not too strenuous but then not too much air there. Feeling great and just wanted to tell you and say thanks...
Implications of FAME Death and MI in the COURAGE study FAME 2 Boden et al., New Engl J Med 2007;356:1503-16.
FAME 2 Stable patients scheduled for one-, two- or three vessel DES stenting FFR in all indicated stenoses There is at least one Stenosis With FFR 0.80 There is no Stenosis with an FFR 0.80 1:1 Randomization PCI+OMT OMT OMT Cohort A Cohort B Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years Primary Endpoint: Death, MI, Urgent TVR at 2 years
January 15 th, 2012
2010 European PCI Guidelines FFR Receives IA Recommendation Wijns W, Kolh P, et al. Eur Heart J 2010; 31:2501-55
Take Home Messages: FFR is an invasive, vessel-specific, lesionspecific index for evaluating the ischemic potential of coronary artery disease. FFR-guided PCI improves outcomes and saves resources. FFR evaluation of patients with multivessel CAD may help guide decision regarding CABG or PCI